Not too long ago most people in the United States and Europe generally avoided excessive exposure to sunlight. Males wore hats that usually included brims large enough to substantially shade the face and neck. At least in the upper and middle classes the typical male garb rarely exposed significant regions of bare skin. Even bathing suits would often cover substantial portions of the male torso including arms and legs—bare chests were unheard of. Females were even more sun protected. Ladies wore large hats complete with veils and scarves. Use of a parasol when outdoors was de rigueur. Female costumes provided even more coverage than male costumes. Until the 1920's even exposed ankles were often considered scandalous. A great premium was placed on delicate white female complexions without any tan or freckling or symptoms of sun exposure.
But the attitude to sun exposure has changed dramatically in the last 50 years or so. First the restrictions on exposure of the male torso were gradually relaxed. Bare arms and legs and even bare chests became acceptable. Today in the western world only coverage of the male genitalia is enforced. At the same time a tan was reevaluated from being a sign of a member of the lower classes to being a sign of vigor and health. A similar but less dramatic transformation also affected the female costume. Bare arms, legs and stomachs became acceptable. Only the female genitalia and to a lesser extent the female bosom remain concealed. It is now considered attractive for females to be tanned and show other symptoms of sun exposure.
Although some exposure to sun light is critical to the synthesis of Vitamin D, sun light is not harmless. Absorption of infra-red light results in heating of the skin and can potentially damage tissues through a “cooking-like” phenomenon. Absorption of visible and ultra-violet light also causes heating, but these wavelengths are much more energetic. Ultra-violet light, and to a lesser extent visible light, are sufficiently energetic to result in chemical changes. The tanning response is largely the skin's attempt to protect itself by providing a shading barrier to sunlight. Although light can induce chemical changes (i.e., damage) to a large variety of biological structures, probably the most significant damage is caused by the ability of ultra-violet light to induce photochemical changes in the pyrimidine bases of DNA (deoxyribonucleic acid). A common expression of this photochemistry is the dimerization of the thymine bases. Such dimerization affects the replication and translation of the genetic material. Cells contain repair mechanisms to excise and replace the damaged regions of DNA, but these mechanisms are not one hundred percent accurate. Therefore, ultra-violet damage introduces mutations into the DNA which can result in abnormal cell growth including precancerous and cancerous lesions.
A common ultra-violet induced lesion occurs when the genetic material of the keratinocytes becomes damaged. Specifically, DNA alterations of keratinocytes in the basal layer of the epidermis result in Actinic Keratoses (AKs). The AKs are crusty, thick, scaly and/or often pigmented premalignant (precancerous) lesions. When abnormal cells spread to or occur in the dermis, the lesion is defined as a squamous cell carcinoma, and the lesion has converted into a true skin cancer. Because a significant number of AKs progress to squamous cell carcinoma, it is important to treat (i.e., remove) AKs. The treatment of Actinic Keratoses (AKs) is very common in dermatology particularly in sunny regions. Increased sun activities over a lifetime increase the risk for these AK's. In Southern California, AKs are very prevalent in the population from the age of 30 years to the elderly.
At the present time, the conventional treatment for AKs is to spray or apply cryogenic liquid nitrogen (LN2) to the lesions. This treatment generally works well for discrete specific lesions; however, the skin can experience sufficient sun damage that AKs will keep appearing even with regular liquid nitrogen treatment. There are some creams that can treat incipient AKs and/or AKs that that are already present. The most common creams contain 5-fluorouracil (5% is the most popular concentration), an anticancer medication. The compound is actually an artificial analog of the DNA base thymidine. It is known as a “suicide inhibitor” because it irreversibly blocks the enzyme thymidylate synthase. Blocking the synthase results in a shortage of thymidine which blocks DNA replication in rapidly growing cancer and precancerous cells thereby resulting in cell death. The reaction to this treatment is typically 4-6 weeks in duration and results in crusted, very painful, very red lesions and peeling of the skin. Even when the 5-fluorouracil treatment is effective, AKs can return and the patient still needs to be followed to watch for further development of AKs.
In my more than 25 years of practicing dermatology, my patients have reported some ultimately positive results from the 5-fluorouracil creams, but most patients would choose not to go through the 4-6 weeks of discomfort and unsightly appearance that results from the treatment.
Current AK treatments are all have significant drawbacks. Liquid nitrogen treatments require regular freezing to the affected areas for adequate control of AKs. LN2 is a common treatment that can be effective in some cases. However, with an increased number of lesions on the face, LN2 treatment can become very traumatic. The freezing hurts and causes scabbing, crusting, blistering and pain for 7-10 days. In addition, it can result in scarring. In some cases, depending on how much sun damage has accumulated over the years or depending on the ongoing sun damage the patient is still receiving (e.g. lifeguards), LN2 treatment is not effective. Furthermore for other body areas, including the scalp or the arms and legs, LN2 treatment is less effective.
The anti-AK creams that are available, notably 5-flourouracil creams, are often very hard on the patient. The treatment results in 4-6 weeks of pain with crusting and scabbing over the entire area of the application, which often includes the entire face. Patients have a very difficult time with the creams if they need to be seen in public for employment purposes or at any social occasion. Many patients who have received 5-flourouracil treatments regret having taken those treatments because of the side effects.
In addition, some patients without obvious onset of squamous cell carcinoma (SCC) or basal cell carcinoma (BCC) show conversion of the AKs to SCC or BCC. With an excessive amount of chronic sun exposure, there is an increase of progression of AKs to skin carcinomas.
Clearly alternate treatments for AKs beyond LN2 and 5-fluorouracil are sorely needed.